Not applicable
1. Field of the Invention
The present invention relates to combinations of pentafluorobenzenesulfonamides and various other chemotherapeutic agents that are capable of inhibiting abnormal cell proliferation.
2. Background
Cancer is a generic name for a wide range of cellular malignancies characterized by unregulated growth, lack of differentiation, and the ability to invade local tissues and metastasize. These neoplastic malignancies affect, with various degrees of prevalence, every tissue and organ in the body. A multitude of therapeutic agents have been developed over the past few decades for the treatment of various types of cancer. The most commonly used types of anticancer agents include: DNA-alkylating agents (e.g., cyclophosphamide, ifosfamide), antimetabolites (e.g., methotrexate, a folate antagonist, and 5-fluorouracil, a pyrimidine antagonist), microtubule disrupters (e.g., vincristine, vinblastine, paclitaxel), DNA intercalators (e.g., doxorubicin, daunomycin), and hormone therapy (e.g., tamoxifen, flutamide). The ideal antineoplastic drug would kill cancer cells selectively, with a wide therapeutic index relative to its toxicity towards non-malignant cells. It would also retain its efficacy against malignant cells, even after prolonged exposure to the drug. Unfortunately, none of the current chemotherapies possess an ideal profile. Most possess very narrow therapeutic indexes and, in practically every instance, cancerous cells exposed to slightly sublethal concentrations of a chemotherapeutic agent will develop resistance to such an agent, and quite often cross-resistance to several other antineoplastic agents.
The development of new anticancer agents has given rise to new treatment regimens and new combinations that are proving more effective in combating this disease.
Accordingly, it is one object of the present invention to provide compositions which directly or indirectly are toxic to actively dividing cells and are useful in the treatment of cancer.
A further object of the present invention is to provide methods for killing actively proliferating cells, such as cancerous, bacterial, or epithelial cells, and treating all types of cancers, and generally proliferative conditions. A further object is to provide methods for treating other medical conditions characterized by the presence of rapidly proliferating cells, such as psoriasis and other skin disorders.
Additional objects, features and advantages will become apparent to those skilled in the art from the following description and claims.
In one aspect, the present invention provides compositions useful for the treatment of cancer and other diseases associated with abnormal cell proliferation. The compositions comprise an antineoplastic agent, including but not limited to prodrugs thereof, pharmaceutically acceptable salts of these agents and a compound having the formula: 
In the formula above, the letter R represents a hydrogen, substituted or unsubstituted (C1-C10)alkyl, or substituted or unsubstituted (C3-C6)alkenyl. The symbol Ar represents a substituted or unsubstituted aryl group or a substituted or unsubstituted heteroaryl group.
Suitable antineoplastic or antiproliferative agents include, but are not limited to, DNA-alkylating agents (e.g., cyclophosphamide, BCNU, busulfan and temozolamide), antimetabolites, antifolates and other inhibitors of DNA synthesis (e.g., methotrexate, 5-fluorouracil, gemcitabine), microtubule disruptors (e.g., vincristine, vinorelbine, paclitaxel, docetaxel), DNA intercalators (e.g., doxorubicin, daunomycin), hormone agents (e.g., tamoxifen, flutamide), topoisomerase I/II inhibitors and DNA repair agents (e.g., hydroxyurea, camptothecin, etoposide), growth factor receptor kinase inhibitors (e.g., AG1478 and AG1296), biological response modifiers (including cytokines such as interferon xcex1 and growth factor inhibitors), antiangiogenic and antivascular agents (e.g., combretastatin A-4), and other agents such as immunoconjugates (e.g., trasuzamab) and antisense oligonucleotides.
The compositions will, in some embodiments, contain a pharmaceutically acceptable carrier or diluent.
In another aspect, the present invention provides methods for the treatment of cancer and other proliferative disorders using the compositions provided above, or using the components in a sequential or simultaneous administration.